Change of lipid peroxide levels in rat tissues after cisplatin administration

Abstract

cis-Diamminedichloroplatinum(II) (cisplatin) is one of the most effective antitumor agents currently available for cancer chemotherapy. Unfortunately, its clinical use is severely limited by its dose-dependent nephrotoxicity. Recently, it has been reported that this nephrotoxicity is associated with an increase in lipid peroxides in the rat kidney. However, it is not clear if the specific nephrotoxicity is related to the increase in lipid peroxides induced by cisplatin since the increase in lipid peroxides in the kidney has not been compared with that in other tissues. We examined the changes in lipid peroxide levels in rat tissues after cisplatin administration to clarify the relationship between lipid peroxides and cisplatin nephrotoxicity. After cisplatin administration (5 mg/kg i.p.), the relative weight of the rat liver decreased, but that of the kidney increased. The increase in lipid peroxide levels in the kidney and liver of cisplatin-treated rats was significant. The percent change from control was greatest in the kidney on the 5th day after administration among all tissues examined. Cisplatin did not affect enzymatic or non-enzymatic lipid peroxidation in microsomes of rat kidney or liver in vitro. It appears that the increase in lipid peroxides in the kidney was not a direct consequence of cisplatin administration.